Table 1. The characteristics of the eligible trials.
| Characteristics | Author (year) |
|||||||
|---|---|---|---|---|---|---|---|---|
| R Fety (1998)14 |
E Gamelin (2008)15 |
O Capitain (2012)16 |
J Grim (2015)27 |
|||||
| BSA arm | PKG arm | BSA arm | PKG arm | BSA arm | PKG arm | BSA arm | PKG arm | |
| Trial | ||||||||
| Study design | Multicenter, randomized, controlled | Multicenter, randomized, controlled | Prospective, controlled | Prospective, controlled, open-label | ||||
| Sample size | 106 | 208 | 157 | 33 | ||||
| Cancer type | Locally advanced head and neck cancer | Metastatic colorectal cancer | Metastatic colorectal cancer | Locally advanced rectal cancer | ||||
| Inclusion and exclusion criteria | Inclusion criteria: Age: 18–75 years; PS: 0–2; Measurable disease; Life expectancy: >3 months; Adequate bone marrow function; Adequate liver function; Adequate renal function; | Inclusion criteria: Measurable lesion; PS: 0–2; Life expectancy: >3 months; adequate hematopoietic function; | Inclusion criteria: Age: >18 years; Measurable lesion; Life expectancy: >3 months; Normal bone marrow and organ function; | Inclusion criteria: Adequate hematopoietic function; Adequate renal function; Adequate liver function; | ||||
| Exclusion criteria: NA | Exclusion criteria: Age: >85 years; Abnormal hematopoietic function; Pregnancy or lactation; History of other malignancy; Neurologic or psychiatric disorder, or cardiac disease or myocardial infarction within the previous 12 months, or serious uncontrolled infections | Exclusion criteria: NA | Exclusion criteria: Uncontrolled arterial hypertension, therapeutic anticoagulation use, pregnancy or lactation, or need for urgent surgery | |||||
| Regimen | 5-FU, cisplatin | 5-FU, leucovorin | FOLFOX | 5-FU, leucovorin | ||||
| Patient | ||||||||
| n | 57 | 49 | 104 | 104 | 39 | 118 | 13 | 20 |
| Male/female | 52/5 | 48/1 | 65/39 | 61/43 | 24/15 | 70/48 | 9/4 | 18/2 |
| Age (range) | 54 (29–72) | 55 (36–69) | 71.2 (50–85) | 71.5 (52–84) | 63 (32–80) | 65 (35–81) | 67.1 | 64.6 |
| Algorithm and dose | ||||||||
| Initial dose (mg/m2) | 4000 | 1500 | 2500 | 2800 | ||||
| Infusion schedule | 96-hour continuous | 8-hour continuous | 46-hour consecutive | 7-day consecutive | ||||
| PK parameter | AUC | Css | Css | Css | ||||
| Target range | 5,760–8,640 ng·h/mL for patients with slow elimination of 5-FU or 10,400–15,600 ng·h/mL for patients with fast elimination of 5-FU | 2,500–3,000 ng/mL | 2,500–3,000 ng/mL | 50–100 ng/mL | ||||
| Final relative dose to the initial (%) | 91.6 | 68.9 | 100 | 51–220 | 75–100 | 60–140 | NA | NA |
| Clinical events, n (%) | ||||||||
| ORR | 44 (77) | 40 (82) | 18 (19) | 35 (39) | 18 (46) | 83 (70) | 1 (8) | 5 (25) |
| Total grade 3/4 ADRs | 16 (28) | 8 (16) | 31 (30) | 18 (17) | 24 (62) | 38 (32) | NA | NA |
| Hematological toxicity | 10 (17) | 4 (8) | 2 (2) | 0 (0) | 14 (35) | 35 (30) | NA | NA |
| Mucositis | 3 (5) | 0 (0) | 2 (2) | 2 (2) | 6 (15) | 1 (1) | NA | NA |
| Digestive toxicity | 3 (5) | 4 (8) | 19 (18) | 4 (4) | 4 (12) | 2 (2) | 4 (32) | 3 (15) |
| Hand-foot syndrome | NA | NA | 7 (7) | 11 (11) | NA | NA | NA | NA |
| Cardiotoxicity | NA | NA | 1 (1) | 1 (1) | NA | NA | NA | NA |
AUC = area under the curve; ADR = adverse drug reaction; BSA = body surface area; Css = steady-state concentration; FOLFOX = Oxaliplatin, 5-FU, leucovorin; NA = not available; PK = pharmacokinetic; PKG = pharmacokinetically guided; PS = performance status; ORR = objective response rate.